Technical Field of the Invention
Embodiments of the invention relate to connection of flexible tubing, and more particularly to an apparatus for substantially sterile connection of flexible tubing. The invention also relates to a method for substantially sterile connection of sterile tubing.
Description of the Related Art
Single use systems, also called disposable systems, are more and more used in the bioprocess industry. For example, separation or reaction systems such as chromatography systems, filter systems, or bioreactor systems have today at least partly been provided as disposable systems. This eliminates the need for cleaning and cleaning validation before processing, in between processes and cycles, or after processing before re-use as required for conventional re-usable equipment. With disposable systems, cross-contamination is avoided. Bioburden control of single-use equipment during manufacturing of the equipment itself is required to eliminate cleaning needs before bringing single-use equipment into product contact. This is usually achieved by manufacturing of single-use equipment in controlled environment (clean room), often followed by sterilisation processes (gamma irradiation). The demands of the level of bioburden control can differ for different applications, however, bioburden control to a certain degree of the equipment is not only required for some applications, but also considered as the preferable option for most of the applications using disposable equipment. The production of this equipment in controlled environments is required to guarantee a low initial level of contaminants prior to the bioburden control procedure, hereby reducing for example endotoxin levels.
Typical applications of aseptic connectors in biomanufacturing are connections between fluid lines, separation units (filters, chromatography columns, adsorbers, membrane adsorbers, expanded or fluidized bed adsorbers), or reaction units (bioreactors, reaction or (bio-) conversion units that for example utilize enzymatic conversions).
Sterility and asepsis are terms used to define the state of a system, a piece of equipment, or a fluid conduit as being in control of bioburden levels to different degrees. Aseptic connectors can be used to interconnect single-use equipment and also single-use equipment and conventional re-use equipment that is bioburden controlled (sanitized, sterilized etc.). Available aseptic connectors are for example ReadyMate™ connectors from GE Healthcare and Kleenpack™ from Pall. These use removable protective films to ensure asepsis and are applied to lengths of tubing and/or equipment in a manufacturing operation, after which the tubing/equipment with the connectors is gamma sterilized. This means that they are only useful for preassembled circuits.
For assembly of tailor-made aseptic circuits directly at the place of use, the current approach is to use heat welding of flexible tubing. Welders for this purpose use electrically heated wafers to cut and weld tubing, and are commercially available from, e.g., GE Healthcare (Sterile Tube Fuser) and Sartorius Stedim Biotech (BioWelder™). The aforementioned equipment are stationary, heavy, and require electrical connection.
Accordingly, there is a need for lighter and more convenient devices to be used in aseptic connection of flexible tubing in, e.g., bioprocessing settings.